Historic characteristics and mortality of patients in the Swiss Amyloidosis Registry.

AIMS OF THE STUDY: Systemic amyloidoses are rare protein-folding diseases with heterogeneous, often nonspecific clinical presentations. To better understand systemic amyloidoses and to apply state-of-the-art diagnostic pathways and treatment, the interdisciplinary Amyloidosis Network was founded in 2013 at University Hospital Zurich. In this respect, a registry was implemented to study the characteristics and life expectancy of patients with amyloidosis within the area covered by the network. Patient data were collected retrospectively for the period 2005-2014 and prospectively from 2015 onwards. METHODS: Patients aged 18 years or older diagnosed with any subtype of systemic amyloidosis were eligible for inclusion if they were treated in one of the four referring centres (Zurich, Chur, St Gallen, Bellinzona). Baseline data were captured at the time of diagnosis. Follow-up data were assessed half-yearly for the first two years, then annually. RESULTS: Between January 2005 and March 2020, 247 patients were screened, and 155 patients with confirmed systemic amyloidosis were included in the present analysis. The most common amyloidosis type was light-chain (49.7%, n = 77), followed by transthyretin amyloidosis (40%, n = 62) and amyloid A amyloidosis (5.2%, n = 8). Most patients (61.9%, n = 96) presented with multiorgan involvement. Nevertheless, single organ involvement was seen in all types of amyloidosis, most commonly in amyloid A amyloidosis (75%, n = 6). The median observation time of the surviving patients was calculated by the reverse Kaplan-Meier method and was 3.29 years (95% confidence interval [CI] 2.33-4.87); it was 4.87 years (95% CI 3.14-7.22) in light-chain amyloidosis patients and 1.85 years (95% CI 1.48-3.66) in transthyretin amyloidosis patients, respectively. The 1-, 3- and 5-year survival rates were 87.0% (95% CI 79.4-95.3%), 68.5% (95% CI 57.4-81.7%) and 66.0% (95% CI 54.6-79.9%) respectively for light-chain amyloidosis patients and 91.2% (95% CI 83.2-99.8%), 77.0% (95% CI 63.4-93.7%) and 50.6% (95% CI 31.8-80.3%) respectively for transthyretin amyloidosis patients. There was no significant difference between the two groups (p = 0.81). CONCLUSION: During registry set-up, a more comprehensive work-up of our patients suffering mainly from light-chain amyloidosis and transthyretin amyloidosis was implemented. Survival rates were remarkably high and similar between light-chain amyloidosis and transthyretin amyloidosis, a finding which was noted in similar historic registries of international centres. However, further studies are needed to depict morbidity and mortality as the amyloidosis landscape is changing rapidly.

Hemodynamics Prior to Valve Replacement for Severe Aortic Stenosis and Pulmonary Hypertension during Long-Term Follow-Up.

(1) Background: Pulmonary hypertension after aortic valve replacement (AVR; post-AVR PH) carries a poor prognosis. We assessed the pre-AVR hemodynamic characteristics of patients with versus without post-AVR PH. (2) Methods: We studied 205 patients (mean age 75 ± 10 years) with severe AS (indexed aortic valve area 0.42 ± 0.12 cm2/m2, left ventricular ejection fraction 58 ± 11%) undergoing right heart catheterization (RHC) prior to surgical (70%) or transcatheter (30%) AVR. Echocardiography to assess post-AVR PH, defined as estimated systolic pulmonary artery pressure > 45 mmHg, was performed after a median follow-up of 15 months. (3) Results: There were 83/205 (40%) patients with pre-AVR PH (defined as mean pulmonary artery pressure (mPAP) ≥ 25 mmHg by RHC), and 24/205 patients (12%) had post-AVR PH (by echocardiography). Among the patients with post-AVR PH, 21/24 (88%) had already had pre-AVR PH. Despite similar indexed aortic valve area, patients with post-AVR PH had higher mPAP, mean pulmonary artery wedge pressure (mPAWP) and pulmonary vascular resistance (PVR), and lower pulmonary artery capacitance (PAC) than patients without. (4) Conclusions: Patients presenting with PH roughly one year post-AVR already had worse hemodynamic profiles in the pre-AVR RHC compared to those without, being characterized by higher mPAP, mPAWP, and PVR, and lower PAC despite similar AS severity.

Corrected QT Interval in Severe Aortic Stenosis: Clinical and Hemodynamic Correlates and Prognostic Impact.

BACKGROUND: The role of the electrocardiogram for risk stratification in patients with severe aortic stenosis is not established. We assessed the hemodynamic correlates and the prognostic value of the corrected QT interval (QTc) in patients with severe aortic stenosis undergoing aortic valve replacement. METHODS: The QT interval was measured in a 12-lead electrocardiogram in 485 patients (age 74 ± 10 years, 57% male) with severe aortic stenosis (indexed aortic valve area 0.41 ± 0.13 cm2/m2, left ventricular ejection fraction 58 ± 12%) the day prior to cardiac catheterization. Prolonged QTc was defined as QTc >450 ms in men and QTc >470 ms in women. The outcome parameter was all-cause mortality. RESULTS: Patients with prolonged QTc (n = 100; 77 men, 23 women) had similar indexed aortic valve area but larger left ventricular and left atrial size, lower left ventricular ejection fraction, more severe mitral regurgitation, lower cardiac index, and higher mean pulmonary artery pressure, mean pulmonary artery wedge pressure, and pulmonary vascular resistance, as compared with patients with normal QTc (n = 385). After a median follow-up of 3.7 years (interquartile range, 2.6-5.2) after surgical (n = 349) or transcatheter (n = 136) aortic valve replacement, patients with prolonged QTc had higher mortality than those with normal QTc (hazard ratio 2.81 [95% confidence interval, 1.51-5.20]; P < .001). Prolonged QTc was an independent predictor of death along with more severe mitral regurgitation and higher pulmonary vascular resistance. CONCLUSIONS: In patients with severe aortic stenosis, prolonged QTc is a marker of an advanced disease stage associated with an adverse hemodynamic profile and increased long-term mortality after aortic valve replacement.

Invasive Hemodynamic Staging Classification of Cardiac Damage in Patients With Aortic Stenosis Undergoing Valve Replacement.

BACKGROUND: An echocardiographic 5-stage classification of cardiac damage in aortic stenosis (AS) has been shown to provide prognostic information. We aimed to create an analogous classification based on invasive hemodynamics. METHODS: We studied 421 patients (age 75 ± 10 years, 59% men) with severe AS with complete invasive hemodynamics obtained before aortic valve replacement (AVR). Cardiac damage stages were defined as follows: stage 0, absence of any of the following criteria; stage 1, left-ventricular end-diastolic pressure >15 mm Hg; stage 2, mean pulmonary artery wedge pressure > 15 mm Hg; stage 3, pulmonary vascular resistance > 3 Wood units and/or systolic pulmonary artery pressure > 60 mm Hg; stage 4, mean right atrial pressure >15 mm Hg. Patients were hierarchically classified in a given stage (worst stage) if the criterion was met for that stage. RESULTS: Sixty-seven (16%) patients were classified as stage 0, 113 (27%) as stage 1, 151 (36%) as stage 2, 73 (17%) as stage 3, and 17 (4%) as stage 4. After a median (interquartile range) follow-up of 3.8 (2.7 to 5.2) years after AVR, mortality was highest in stage 4 (hazard ratio; 95% confidence interval: 6.17 (1.74-21.89) vs stage 0; P = 0.005 and stage 3 patients (hazard ratio; 95% confidence interval: 4.17 (1.39-12.49) vs stage 0; P = 0.01,whereas mortality did not differ between patients in stages 0 to 2. CONCLUSIONS: A staging system of cardiac damage based on invasive hemodynamic parameters in patients with severe AS undergoing AVR predicts mortality. Pulmonary vascular disease and high right-atrial pressure are the major drivers of mortality.

Hemodynamic profile of patients with severe aortic valve stenosis and atrial fibrillation versus sinus rhythm.

BACKGROUND: In patients with severe aortic stenosis (AS), atrial fibrillation (AF) is associated with increased long-term mortality after aortic valve replacement (AVR), which may be due to unfavorable hemodynamics in AF. We aimed to analyze the hemodynamic profile of patients with severe AS and AF versus sinus rhythm (SR). METHODS: We performed cardiac catheterization in 486 patients (age 74 ±â€¯10 years, 58% males) with severe AS [indexed aortic valve area 0.41 ±â€¯0.13 cm2, left ventricular ejection fraction 58 ±â€¯12%]: 50 patients had AF, and 436 patients had SR. All patients underwent surgical (n = 350) or transcatheter (n = 136) AVR. RESULTS: Despite similar indexed aortic valve area (0.41 ±â€¯0.11 vs. 0.41 ±â€¯0.12 cm2/m2; p = 0.45) patients with AF had lower left ventricular ejection fraction, larger left atrial size, lower tricuspid annular plane systolic excursion, higher mean pulmonary artery pressure (34 ±â€¯13 vs. 24 ±â€¯9 mmHg), mean pulmonary artery wedge pressure (mPAWP; 22 ±â€¯8 vs. 15 ±â€¯7 mmHg), and pulmonary vascular resistance (2.8 ±â€¯1.9 vs. 2.0 ±â€¯1.3 Wood units) and lower stroke volume index (26 ±â€¯9 vs. 37 ±â€¯10 ml/m2) than patients with SR (p < 0.05 for all). Patients with AF and SR had a different mPAWP-left ventricular end-diastolic pressure (LVEDP) relationship with higher mPAWP in AF and higher LVEDP in SR. After a median follow-up of 49 (interquartile range, 35-64) months post-AVR patients with AF (p = 0.05) and patients with a larger difference between mPAWP and LVEDP (p = 0.005) had higher mortality. CONCLUSIONS: Patients with severe AS and concomitant AF have a distinct and significantly worse hemodynamic profile compared to patients with SR associated with worse clinical outcome.

Relationship between B-type natriuretic peptide and invasive haemodynamics in patients with severe aortic valve stenosis.

AIMS: In patients with aortic stenosis (AS), B-type natriuretic peptide (BNP) is a prognostic marker. However, there is little information on the association between BNP and invasive haemodynamics in AS. The aim of the present study was to assess the hitherto not well-defined relationship between BNP and invasive haemodynamics in patients with severe AS undergoing aortic valve replacement (AVR) with a view to understand the link between high BNP and poor prognosis in these patients. In particular, we were interested in the association between BNP and combined pre-capillary and post-capillary pulmonary hypertension (CpcPH). METHODS AND RESULTS: BNP was measured in 252 patients (age 74 ± 10 years, 58% male patients) with severe AS [indexed aortic valve area 0.4 ± 0.1 cm2 /m2 and left ventricular ejection fraction (LVEF) 57 ± 12%] the day before cardiac catheterization. Patients were followed for a median (interquartile range) period of 3.1 (2.3-4.3) years after surgical (n = 157) or transcatheter (n = 95) AVR. The prevalence of CpcPH (mean pulmonary artery pressure ≥ 25 mmHg, mean pulmonary artery wedge pressure > 15 mmHg, and pulmonary vascular resistance > 3 Wood units) was 13%. The median BNP plasma concentration was 188 (78-452) ng/L. The indexed aortic valve area was similar across BNP quartiles (P = 0.21). Independent predictors of higher BNP (ln transformed) included lower haemoglobin (beta = -0.18; P < 0.001), lower LVEF (beta = -0.20; P < 0.001), more severe mitral regurgitation (beta = 0.20; P < 0.001), higher mean pulmonary artery wedge pressure (beta = -0.37; P < 0.001), and higher pulmonary vascular resistance (beta = 0.21; P < 0.001). In a multivariate model with CpcPH rather than its haemodynamic components, CpcPH was independently associated with higher BNP (0.21; P < 0.001). Higher ln BNP was associated with higher mortality [hazard ratio 1.90 (95% confidence interval 1.33-2.71); P < 0.001] in the univariate analysis. Patients in the third and fourth BNP quartiles had a more than six-fold risk of death compared with patients in the first and second quartiles [hazard ratio 6.29 (95% confidence interval 1.86-21.27); P = 0.003]. In the multivariate analysis, lower LVEF [hazard ratio 0.96 (95% confidence interval 0.94-0.99) per 1% increase; P = 0.01] and CpcPH [hazard ratio 4.58 (95% confidence interval 1.89-11.09); P = 0.001] but not BNP were independently associated with mortality. The areas under the receiver operator characteristics curve for BNP for the prediction of CpcPH and mortality were 0.88 and 0.74, respectively. CONCLUSIONS: In patients with severe AS, higher BNP is a marker of the presence of CpcPH and its contributors. The association between BNP and such an adverse haemodynamic profile at least in part explains the ability of BNP to predict long-term post-AVR mortality.

Use of coronary computed tomography angiography in clinical practice - single centre experience in Switzerland in light of current recommendations based on pretest probability considerations.

AIMS OF THE STUDY: Coronary computed tomography angiography (CCTA) is recommended as a first-line option for the exclusion of coronary artery disease in patients with low to intermediate (15–50%) pretest probability. We aimed to study the use of CCTA in clinical practice in a single centre in Switzerland in light of this recommendation. METHODS: In 523 consecutive patients (age 56 ± 13 years, 48% females) undergoing CCTA during a period of 2 years, the pretest probability of coronary artery disease was assessed using the revised Diamond-Forrester model (CAD consortium score). In patients who had invasive coronary angiography following CCTA, angiographic findings and the consequences regarding management are reported. RESULTS: The majority of patients (n = 316; 60%) had a pretest probability <15%, 188/523 (36%) had a pretest probability between 15 and 50%, and 19/523 (4%) had a pretest probability >50%. The prevalences of coronary artery disease (≥50% lumen diameter reduction) by CCTA in patients with pretest probability <15%, 15–50%, and >50% were 25/316 (8%), 45/188 (24%) and 8/19 (42%), respectively. In 438/523 patients (84%), a CCTA scan showing no coronary artery disease represented the final diagnostic step. In patients undergoing invasive coronary angiography (n = 59, age 58 ± 9 years, 88% with coronary artery disease by CCTA), coronary artery disease was found in 47/59 (80%) patients and 36/59 (61%) patients underwent revascularisation. The prevalences of coronary artery disease by invasive coronary angiography in patients with pretest probability <15%, 15–50%, and >50% were 14/21 (67%), 28/32 (88%) and 5/6 (83%). CONCLUSIONS: The present data suggest that the currently used pretest probability model is still imperfect and that guideline recommendations regarding pretest probability use for the selection of CCTA candidates are not followed completely. Still, in more than 80% of patients coronary artery disease could be excluded by CCTA, while CCTA also detected a significant number of patients with coronary artery disease in the low pretest probability population. Thus, the data suggest a very judicious use of CCTA as a gatekeeper for invasive coronary angiography in current practice.

Patterns of Incidence Rates of Cardiac Complications in Patients With Congenital Heart Disease.

BACKGROUND: This study aimed to evaluate age at the first onset of cardiac complications and variation of frequency of complications between different congenital heart defects. METHODS: The analysis included participants of the Swiss Adult Congenital Heart Disease Registry (SACHER). For this study, cardiac complications up to the time of inclusion in SACHER were analysed. Complications included atrial fibrillation, atrial flutter, supraventricular tachycardia, ventricular tachycardia, complete heart block, heart failure, stroke, endocarditis, myocardial infarction, and pulmonary hypertension. Incidence rates (IR; incidence rate per 1000 patient-years) for different age categories and diagnosis groups were analysed. RESULTS: Of 2731 patients (55% male, mean age 34 ± 14 years, 92,349 patient-years), a total of 767 (28%) had experienced at least 1 cardiac complication. The majority of complications (550; 72%) occurred in adulthood (> 18 years). Apart from perioperative stroke (IR: 1.77 in age group ≤ 4 years) and complete heart block (IR: 2.36 in age group ≤ 4 years), IR were much lower in childhood (IR < 1 for all complications between 5 and 17 years). Incidence of cardiac complications increased during adult life with highest IR for atrial fibrillation and atrial flutter in the age group ≥ 50 years (IR: 17.6 and 9.7, respectively). There were important variations of the distribution of complications among different diagnosis groups. CONCLUSIONS: Cardiac complications are frequent in congenital heart disease. Apart from perioperative stroke and complete heart block, IR are low in childhood but the incidence increases during adult life. These data underscore the need of lifelong follow-up and may help for better allocation of resources maintaining follow-up.

Impact of Advanced Modeled Iterative Reconstruction on Coronary Artery Calcium Quantification.

RATIONALE AND OBJECTIVES: To evaluate the influence of advanced modeled iterative reconstruction (ADMIRE) on the coronary artery calcium (CAC) scores by computed tomography (CT). MATERIALS AND METHODS: Sixty patients underwent CAC imaging with dual-source 192-slice CT. Agatston, volume and mass score were calculated from filtered back projection (FBP) and iterative reconstructions with different levels of ADMIRE. Friedman test and Wilcoxon rank sum test were used for multiple comparisons of CAC values and the difference ratio among different ADMIRE groups using FBP as reference. RESULTS: The median Agatston score (range) using FBP was 115 (0.1-3047) and significantly decreased with incremental ADMIRE levels 1-5: 96 (0.1-2813), 91 (0-2764), 87 (0-2699), 80 (0-2590), 70 (0-2440); all P < 0.001. In comparison with FBP Agatston, volume and mass scores significantly decreased with increasing ADMIRE levels 1-5 (P < 0.001): from -12% to -39%, from -14% to -41%, and from -13% to -40%, respectively. In four patients with low calcium burden, the use of ADMIRE 2 or higher resulted in the disappearance of calcium that was detectable using FBP or ADMIRE 1. The decrease of CAC in high-level ADMIRE resulted in a reassignment to a lower Agatston risk group in 27%. CONCLUSIONS: ADMIRE causes a substantial reduction of the CAC scores measured by cardiac CT, which leads to an underestimation of cardiovascular risk scores in some patients.

Prevalence, extent, and independent predictors of silent myocardial infarction.

BACKGROUND: The phenomenon of silent myocardial infarction is poorly understood. METHODS: We aimed to evaluate the prevalence, extent, and independent predictors of silent myocardial infarction in 2 large independent cohorts of consecutive patients without a history of myocardial infarction referred for rest/stress myocardial perfusion single photon emission computed tomography. There were 1621 patients enrolled in the derivation cohort and 338 patients in the validation cohort. Silent myocardial infarction was diagnosed in patients with a myocardial scar ≥5% of the left ventricle. RESULTS: In the derivation cohort, the prevalence of silent myocardial infarction was 23.3% (n = 377). The median infarct size was 10% (interquartile range [IQR] 5%-15%) of the left ventricle. The prevalence of silent myocardial infarction was 28.5% in diabetics and 21.5% in nondiabetics (P = .004). Diabetes mellitus was an independent predictor for the presence of silent myocardial infarction (odds ratio 1.5; 95% confidence interval, 1.1-1.9; P = .004). These findings were confirmed in the independent validation cohort. In the validation cohort, the prevalence of silent myocardial infarction was 26.3% (n = 89), while the prevalence was higher in diabetics (35.8%) than in nondiabetics (24%; P = .049). The median infarct size was 11.8% (IQR 5.9%-17.6%) of the left ventricle. Again, in logistic regression analysis, diabetes mellitus was a significant predictor of the presence of silent myocardial infarction. CONCLUSION: Silent myocardial infarctions are more common than previously thought. One of 4 patients with suspected coronary artery disease had experienced a silent myocardial infarction; the extent in average is 10% of the left ventricle, and it is more common in diabetics.

How to evaluate physical fitness without a stress test?

To assess cardiorespiratory fitness (CF), usually a stress test is necessary. Our aims were to assess CF in a patient population with suspected or known coronary artery disease (CAD) based on a questionnaire (quest); to compare estimated CF with achieved workloads, and to evaluate its prediction of stress modality (physical/pharmacologic). Consecutive 612 patients undergoing myocardial perfusion SPECT (MPS) completed quest. They first chose one category which best described their daily physical activities. The second part contained patient characteristics (gender, age, BMI, and resting heart rate). An activity score was calculated and metabolic equivalents (METs) were estimated. Estimated and achieved results were compared. Patients with pharmacologic test (n = 208) provided a lower estimate of their performance than physically stressed patients (n = 404): 7.0 ± 2.1 and 8.2 ± 2.3 METs, respectively (P < 0.0001). The latter showed a good correlation between estimated and achieved METs (r = 0.63, P < 0.0001). Regarding prediction of the stress modality, area under the curve (ROC) was 0.65 (P < 0.0001). The quest can easily be applied in daily practice to assess CF in a patient population with CAD and for estimating whether an adequate physical stress test can be carried out.

Diabetes reduces left ventricular ejection fraction--irrespective of presence and extent of coronary artery disease.

BACKGROUND: It is not clear whether diabetes reduces systolic left ventricular function (left ventricular ejection fraction, LVEF) irrespective of coronary artery disease (CAD). The aim of this study was to compare the LVEF between diabetic and non-diabetic patients with respect to the extent of CAD. METHODS AND RESULTS: Consecutive patients undergoing stress myocardial perfusion SPECT (MPS) were evaluated. MPS was interpreted using a 20-segment model with a five-point scale to define summed stress score (SSS), summed rest score, and summed difference score. LVEF was measured by gated SPECT and then compared with respect to diabetic status and SSS categories. Of 2635 patients, data of 2400 was available. Of these, 24% were diabetic, mean age was 64±11y, and 31% were female. Diabetics had a significantly lower LVEF compared with non-diabetics regardless of the extent of CAD: 53±13 and 55±13% respectively (P=0.001). Diabetics and non-diabetics did not differ significantly in the distribution of SSS categories. Diabetes was an independent predictor of decreased LVEF (odds ratio 1.6, 95% confidence interval 1.2-2.0; P<0.001). CONCLUSION: Diabetics had a lower LVEF than non-diabetics. This difference could be demonstrated regardless of CAD extent and might in part explain their generally worse cardiac survival compared with non-diabetics on an epidemiological level. In addition, this finding points to discussed mechanisms other than CAD lowering LVEF in diabetics.